Whole-body and targeted narrowband ultraviolet B phototherapy effectively stabilize acral vitiligo with negligible repigmentation beyond wrists and ankles: Results from a split-body randomized controlled trial.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy promotes stability and repigmentation in vitiligo. No studies have compared targeted NB-UVB with whole-body NB-UVB in treatment of acral vitiligo. OBJECTIVES: This randomized split-body study compared whole-body NB-UVB with targeted NB-UVB in inducing stability and repigmentation in acral vitiligo. METHODS: Thirty-two patients with bilaterally symmetrical acral vitiligo lesions (distal to elbows and knees) were recruited. Patients received whole-body NB-UVB treatment, with one hand and one foot shielded until elbow and knee, followed by targeted NB-UVB treatment on the shielded side. Patients were assessed at 4-week intervals for 24 weeks using Vitiligo Disease Activity (VIDA) score, Vitiligo Skin Activity Score (VSAS), Vitiligo Area Scoring Index (determined through fingertip method, using the method to calculate facial-VASI) and degree of repigmentation. RESULTS: After 12 weeks, 87.5% of patients achieved a VIDA score of 3, with none having active disease at 24 weeks. Over 50% repigmentation was observed in 42.2% and 37.5% of limbs in whole-body and targeted groups, respectively (p = .95). No improvement in F-VASI scores of hands and feet (distal to wrist and ankles) was noted with either modality over the 24-week period. CONCLUSION: Our study showed comparable repigmentation rates between whole-body and targeted NB-UVB groups. Limited effectiveness of phototherapy in repigmentation of hands and feet underscores an important therapeutic gap.

308 nm excimer laser and tacrolimus ointment in the treatment of facial vitiligo: a systematic review and meta-analysis.

This study aimed to investigate the effects and safety of 308 nm excimer laser (308 nm EL) and tacrolimus ointment (TO) in the treatment of facial vitiligo (FV). We searched Cochrane Library, PUBMED, EMBASE, CNKI, and WANGFANG from inception to June 1, 2023. Outcomes included overall response rate (ORR), total adverse reaction rate (TARR), recurrence rate at 3-month (RR-3) and recurrence rate at 6-month (RR-6). The outcome data were presented as odds ratios (OR) with 95% confidence intervals (CI). The risk of bias was assessed by Cochrane risk-of-bias tool and data analysis was performed by RevMan 5.4 software. This study included a total of 19 trials involving 2085 patients. When comparing 308 nm EL monotherapy with 308 nm EL plus TO, significant differences in the ORR (OR = 4.29, 95% CI [2.97, 6.19], I2 = 0%, P < 0.001), RR-3 (OR = 0.18, 95% CI [0.05, 0.69], I2 = 0%, P = 0.01), and RR-6 (OR = 0.38, 95% CI [0.14, 1.03], I2 = 39%, P = 0.06) were found between the two managements. When comparing TO monotherapy with TO plus 308 nm EL, its results showed significant differences in the ORR (OR = 4.21, 95% CI [2.90, 6.11], I2 = 0%, P < 0.001), TARR (OR = 0.42, 95% CI [0.22, 0.81], I2 = 4%, P = 0.009), and RR-3 (OR = 0.32, 95% CI [0.01, 8.03], P = 0.49) between the two modalities. The results of this study suggest that the combination of 308 nm EL and TO is more effective than either treatment alone for the treatment of FV.

Efficacy of prostaglandin E2 versus prostaglandin F2 alpha assisted with narrowband-UVB in stable vitiligo.

In the recent decades, prostaglandins were recommended as a new therapeutic modality of stable vitiligo with promising efficacy. Therefore, we designed the current work to compare the significance of two different subtypes of prostaglandins [prostaglandin E2 (PGE2) versus prostaglandin F2 alpha (PGF2α)], assisted with NB-UVB phototherapy, in treatment of stable vitiligo. This study was conducted on 30 patients with stable non-segmental vitiligo. Three approximately similar vitiliginous areas were chosen in each patient and assigned into 3 groups. Each group treated with intradermal injection of either PGE2 (group I), PGF2α (group II), or saline as placebo (group III) at frequency once/week for 12 weeks. Concomitantly, all groups received NB-UVB phototherapy twice weekly for 3 months. The outcomes of this study discovered that the therapeutic efficacy of intradermal injection of either PGE2 or PGF2α assisted with NB-UVB phototherapy was comparable with non-significant difference between them in spite of being significantly higher than NB-UVB alone. However, there were a significantly earlier onset of repigmentation and higher degree of satisfaction regarding areas treated with PGE2 than those treated with PGF2α. In conclusion, both PGF2α and PGE2 intradermal injection could be considered as quite simple and affordable techniques in the treatment of stable vitiligo with no reported side effects and good patient satisfaction.

Clinical effect of stem cell transplantation combined with 308-nm excimer laser therapy for 56 cases of vitiligo.

OBJECTIVE: To probe the clinical effect of stem cell transplantation in combination with 308-nm excimer laser therapy for vitiligo and to analyze its value in clinical application. METHODS: A total of 56 patients with stable non-segmental vitiligo in different parts who were not cured by other therapies visiting our hospital from March 2019 to December 2021 were enrolled as study subjects. They were treated by stem cell transplantation combined with 308-nm excimer laser therapy. The treatment efficacy was observed and analyzed. RESULTS: Among the 56 patients, 38 (67.85%) and 49 (87.5%) patients were cured at 6 and 12 months after treatment, respectively. CONCLUSION: Stem cell transplantation combined with 308-nm excimer laser therapy for vitiligo achieves significant efficacy, with the cure rate far superior to that of other therapies for vitiligo. The therapy is worthy of popularization in the clinic.

The efficacy of bimatoprost ophthalmic solution combined with NB-UVB phototherapy in non-segmental and segmental vitiligo: a single-blind randomized controlled study.

Bimatoprost ophthalmic solution 0.03% (PGF2α analogues) combined with narrowband ultraviolet B (NB-UVB) was reported to be an effective treatment for vitiligo. To investigate the efficacy and safety of treatment for non-segmental/segmental vitiligo compared among bimatoprost ophthalmic solution 0.01% combined with NB-UVB phototherapy, bimatoprost monotherapy, and placebo. This single-blind randomized controlled study enrolled stable Thai vitiligo patients with at least three similarly sized lesions in the same anatomical area. The treatment duration was 6 months with 1- and 2-month post-treatment follow-ups. The 3 selected lesions on each patient were randomized to receive combination therapy, monotherapy, or placebo. The Vitiligo Area Scoring Index (VASI) was used to evaluate lesion response. Of the 25 initially enrolled subjects, 19 patients were analyzed. There were 13 and 6 non-segmental and segmental vitiligo cases, respectively. Eight and 11 cases had face/neck and non-face/neck lesions, respectively. Non-segmental vitiligo and non-face/neck vitiligo patients in the combination group had significant improvement in VASI score at 3 months, 6 months, and at the 2-month follow-up. No side effects were observed/reported. Bimatoprost combination therapy was shown to be safe and effective for treating Thai patients with non-segmental vitiligo in non-face/neck areas of the body.

Acceleration of melanocyte senescence by the proinflammatory cytokines IFNγ and TNFα impairs the repigmentation response of vitiligo patients to narrowband ultraviolet B (NBUVB) phototherapy.

Vitiligo is a chronic autoimmune disease characterized by the T helper 1 (Th1) cytokine-driven immune destruction of melanocytes (MCs). Although narrowband ultraviolet B (NBUVB) phototherapy has been proven to be an effective therapeutic option, the repigmentation response to that phototherapy varies greatly in different vitiligo patients. Here, we demonstrate that there is an increase of NBUVB-induced cellular senescence in vitiligo MCs exposed to Th1 cytokine interferon γ (IFNγ) and/or tumor necrosis factor α (TNFα) in lesional vitiligo skin from poor responders who had undergone NBUVB phototherapy. Supplementation with exogenous recombinant human stem cell factor (rhSCF) in the culture medium as well as the lentiviral vector-mediated overexpression of cKIT could prevent the MCs from the IFNγ/TNFα-accelerated cellular senescence. Mechanistic studies indicated that the reduced ratio of membrane-bound KIT (mKIT) to the soluble form of KIT (sKIT) is directly related to the cellular senescence of vitiligo MCs following exposure to IFNγ and TNFα. Furthermore, the matrix metalloprotease 9 (MMP9) inhibitor GM6001 attenuates the production of sKIT via the suppression of cKIT ectodomain shedding. Altogether, our study indicates that the presence of Th1 cytokines IFNγ and/or TNFα in the epidermal milieu might impair the repigmentation response of vitiligo patients to NBUVB phototherapy.

Contributions of NR1H3 genetic polymorphisms to susceptibility and effects of narrowband UVB phototherapy to nonsegmental vitiligo.

Vitiligo is the most common depigmenting disorder to which both genetic and environmental factors contribute. The aim of the current work was to evaluate the relationship between polymorphisms of the gene nuclear receptor subfamily 1 Group H member 3 (NR1H3) and the risk of vitiligo and phototherapy effects in the Chinese Han population. Two independent samples were enrolled to form the discovery set (comprised of 1668 nonsegmental vitiligo [NSV] patients and 2542 controls) and the validation set (comprised of 745 NSV patients and 1492 controls). A total of 13 tag single nucleotide polymorphisms (SNPs) were genotyped in the samples from the discovery stage. SNPs that achieved nominal significance were validated in another independent sample set. The serum level of NR1H3 protein was assayed using enzyme-linked immunosorbent assay kits in the validation set. Genetic association analysis was carried out at allelic and genotypic levels. The therapeutic effects of significant SNPs were examined in the validation set. The SNP rs3758672 was significantly associated with NSV. The A allele was correlated with NSV risk and poorer therapeutic effects. The A allele was strongly correlated with the increased level of serum NR1H3 in both controls and patients. In summary, SNP rs3758672 in NR1H3 was significantly associated with both disease susceptibility and individualized therapeutic effects of NSV in study participants with Han Chinese ancestry.

Surrounding Needling and Narrowband Ultraviolet B Phototherapy Treatment: Synergistic Effects for Repigmentation in Chronic, Stable Nonsegmental Vitiligo.

Context: Narrowband ultraviolet B (NBUVB) phototherapy is the standard treatment for chronic stable vitiligo, but its efficacy, when used alone, is often unsatisfactory. Objective: The study evaluated the efficacy of surrounding needling with acupuncture needles in combination with NBUVB phototherapy for lesions on different body parts of patients with chronic stable vitiligo. Design: The research team designed a 12-week, randomized, open-label, prospective, intra-individual, comparative clinical trial. Setting: The study took place in the Department of Dermatology at Shin-Kong Wu Ho-Su Memorial Hospital in Taiwan. Participants: Participants were patients at the hospital, aged 20-80 years, with chronic stable nonsegmental vitiligo. The lesions on both sides of their bodies had the same baseline conditions. Nine patients with 14 pairs of lesions (n = 28) were included in the study, and eight participants with 13 pairs of lesions (n = 26) successfully completed the study. Intervention: Vitiligo lesions in the intervention group were treated with surrounding needling combined with NBUVB phototherapy, whereas the control group received NBUVB phototherapy only. Outcome Measures: The primary outcome was evaluated at Week 12 using the modified Vitiligo Area Scoring Index (VASI), which focuses on local depigmentation only without multiplication by body surface area, and the testing used the Wilcoxon signed-rank test. A higher VASI score indicates more severe vitiligo. Pain was rated postintervention, after completion of all treatments. Results: At baseline, the modified VASI score in both groups was 93.07 ± 4.62. Postintervention, this score in the intervention group improved to 78.46 ± 15.24, with a significant difference between baseline and postintervention (P = .007), and in the control group, the score improved to 91.92 ± 6.67, with no significant difference having occurred (P = .317). A statistically significant difference was found between the intervention group and the control group in the change in scores postintervention (P = .007). Conclusion: Surrounding needling in combination with NBUVB phototherapy may be a promising treatment for chronic stable nonsegmental vitiligo. Future studies with larger sample sizes and long-term follow-up are warranted.

Apremilast and narrowband ultraviolet B combination therapy suppresses Th17 axis and promotes melanogenesis in vitiligo skin: a randomized, split-body, pilot study in skin types IV-VI.

Improved repigmentation of generalized vitiligo in skin types IV-VI has been reported in clinical response to combined therapy with apremilast and narrowband (NB)-UVB; however, tissue responses to combined therapy versus NB-UVB monotherapy have not been elucidated. We compared the change from baseline in cellular and molecular markers in vitiligo skin after combined therapy versus NB-UVB monotherapy. We assessed lesional and nonlesional skin samples from enrolled subjects and evaluated for immune infiltrates, inflammatory, and melanogenesis-related markers which were compared across different treatment groups. Combined therapy resulted in significant reduction of CD8+T cells and CD11c+ dendritic cells, downregulation of PDE4B and Th17-related markers, and upregulation of melanogenesis markers. This study was limited to small sample size, skin types IV-VI, and high dropout rate. Our molecular findings support the clinical analysis that apremilast may potentiate NB-UVB in repigmentation of generalized vitiligo in skin types IV-VI.

Evaluation of vitamin D receptor gene polymorphisms (ApaI and TaqI) as risk factors of vitiligo and predictors of response to narrowband UVB phototherapy.

Vitiligo is acquired depigmentation due to multiple factors. Vitamin D in skin, through its receptors (VDR), regulates cell growth, differentiation, immune response and exerts both stimulatory and protective effects on melanocytes. The gene sequence encoding VDR has polymorphic forms such as ApaI and TaqI that may affect vitamin D actions. Narrowband ultraviolet B (NB-UVB) phototherapy became the mainstay of vitiligo treatment because of its efficacy and little side effects. The current work aimed at evaluating the possible association between VDR gene polymorphisms (TaqI and ApaI) and susceptibility of vitiligo and if they could be predictors of response to NB-UVB phototherapy in Egyptian vitiligo patients. 100 vitiligo patients indicated for NB-UVB phototherapy and 100 healthy age and sex matched controls were included. All participants were subjected to history taking, general and dermatological examinations, and VDR ApaI and TaqI gene polymorphisms analysis by PCR-RFLP. The patients received NB-UVB 3times per week for 6 months then revaluated. There was significant increase in Aa genotype of ApaI polymorphism in patients associated with significant increase in vitiligo activity. 66% of patient showed variable degrees of response to NB-UVB. The responders significantly had AA genotype of ApaI polymorphism. TaqI polymorphism showed nonsignificant effects on vitiligo susceptibility and response to NB-UVB. A allele of ApaI was significant independent predictor of NB-UVB phototherapy responders. VDR gene polymorphism (ApaI) may share in vitiligo pathogenesis and response to NB-UVB. Knowing the genetic background of the patient helps individualization of treatment to get better results.